Associação entre polimorfismos dos genes APOE, BDNF, DCHS2 e GAB2 com o risco e os endofenótipos relacionados ao Comprometimento Cognitivo Leve Amnéstico e à demência de Alzheimer

Abstract

The late onset form of Alzheimers disease (AD) is complex and heterogeneous and there are several genetic polymorphisms that interact each other and with non-genetic factors influencing its susceptibility. The main established genetic risk factor is the 4 allele of the apolipoprotein E (APOE). The amnestic form of the Mild Cognitive Impairment (aMCI) is a heterogeneous syndrome that represents an intermediate stage between cognitive changes from normal aging and dementia. The aMCI characterizes only by memory impairment single domain aMCI - or associated with other cognitive impairments multiple domains aMCI. The aMCI is a risk factor for progression to AD. In this cross-sectional study we aimed to study the impact of genetic polymorphisms of four genes (APOE, BDNF, DCHS2 e GAB2), and socio-demographic and clinic factors on the risk of developing AD and its endophenotypes - age-at-onset of disease and performance on cognitive tests (MMSE and Mattis Dementia Rating Scale). 536 elderly subjects were selected, submitted to the same research protocol and divided into three groups: controls, aMCI and AD. Our results demonstrated an association of type 2 diabetes mellitus and aMCI; dyslipidemia and aMCI only in women; advanced age and low level of education with AD and between arterial hypertension and AD only in 4 non-carrier subgroup. Regarding the genetic polymorphisms, the DCHS2 and APOE genes were associated with aMCI and AD. The 4 allele was correlated with an earlier onset of AD. We also observed that BDNF and APOE genes influenced the cognitive performance of controls and aMCI individuals.